MRI evidence of microstructural lesions in the mesencephalon and pons of patients with idiopathic narcolepsy

Introduction: Neuroimaging in patients with symptomatic narcolepsy often reveals hypothalamic, pontine or mesencephalic lesions. However, the relevance of these findings for patients with idiopathic narcolepsy remains unclear and previous neuroimaging studies revealed conflicting results.

Material and Methods: To investigate possible microstructural abnormalities in narcolepsy patients, Diffusion Tensor Imaging (DTI) was conducted on nine patients with idiopathic narcolepsy without RBD and nine healthy control subjects. Whole-head DTI data were analysed without an a-priori hypothesis. Voxelwise statistical analysis of the fractional anisotropy (FA) data was performed using the novel, non-linear analysis approach Tract-Based Spatial Statistics (TBSS).

Results: DTI results revealed microstructural changes in the mesencephalon and the pons of patients with idiopathic narcolepsy. Additionally, areas in the middle frontal gyrus, olfactory cortex, lingual gyrus, cuneus, superior and inferior temporal gyrus as well as the frontal and parietal white matter and the caudate nucleus had altered microstructure in patients with narcolepsy.

Fig.1: Microstructural changes in the pons and mesencephalon in patients with idiopathic narcolepsy

Conclusion: Our DTI study shows widespread microstructural changes that are not visible on conventional, clinical routine MRI in patients with idiopathic narcolepsy. The microstructural changes in the pons and mesencephalon in patients with idiopathic narcolepsy suggest that pontine and mesencephalic areas regulating REM sleep might be involved in idiopathic narcolepsy as well as symptomatic narcolepsy and might represent changes in hypocretin projections to these areas.